Simultaneous measurements of membrane potential and intracellular Ca2+ were used to study the effects of hypoxia on striatal and cortical neurones. Striatal neurones responded to hypoxia with a reversible membrane depolarization coupled with a transient increase in intracellular Ca2+. Thirty minutes of hypoxia caused an irreversible membrane depolarization associated with a massive raise in Ca2+ levels, leading to cell death. Conversely, cortical neurones were more resistant to O2 deprivation. Hypoxia (4-10 min) induced minimal changes in both membrane potential and Ca2+ signals. Longer periods (20-30 min) caused an initial membrane hyperpolarization followed by a large but reversible depolarization coupled with a transient increase in Ca2+ signals. These results support the hypothesis of a differential sensitivity of central neurones to hypoxia, suggesting that striatal neurones are more vulnerable than cortical cells.